儿童社区获得性肺炎肺外并发症早期预警指标研究进展

Research progress on early warning of extrapulmonary complications in pediatric community-acquired pneumonia

摘要

儿童社区获得性肺炎（CAP）是威胁全球儿童健康的重要感染性疾病，肺外并发症可累及消化、神经、心血管、血液及皮肤黏膜等多个系统，显著增加患儿进展至重症甚至死亡的风险。儿童 CAP 肺外并发症的发病机制复杂多样，涉及病原体直接侵袭、免疫介导损伤、炎症因子风暴及微循环障碍，其中免疫与炎症的相互作用是核心环节。不同病原体的致病机制也存在差异，免疫介导损伤与炎症因子风暴的相互促进，是重症 CAP 引发多系统肺外并发症的核心病理环节。消化系统并发症以肝损伤最常见，预警指标包括白细胞介素 1（IL-1）>28.35 pg/mL、IL-6>24.9 pg/mL、C 反应蛋白（CRP）>34.6 mg/L 等，不同病原体（如肺炎支原体、鹦鹉热衣原体）有其特异性指标。神经系统并发症中，脑炎、脑病及癫痫发作多见，预警指标有神经丝轻链（NFL）、脑脊液乳酸、D-二聚体及淋巴细胞计数等。心血管系统以心肌损伤为主（发生率约 30.1%），预警指标包括 IL-6≥258.64 pg/mL、CRP≥14.27 mg/L、中性粒细胞与淋巴细胞比值（NLR）≥2.41 等，新型标志物可溶性生长刺激表达基因 2（sST2）和循环游离 DNA（cfDNA）亦具价值。血液系统严重并发症如弥散性血管内凝血（DIC）和噬血细胞综合征（HLH），预警指标有血清乳酸脱氢酶与白蛋白比值（LAR）≥8.08、甘油三酯>3.02 mmol/L 等。皮肤黏膜损害多与肺炎支原体相关，表现为皮疹和黏膜炎。目前预警指标尚需多中心大样本验证，且多数研究聚焦肺炎支原体，未来应加强多病原体比较及多组学研究，建立标准化评估体系。

Abstract

Pediatric community-acquired pneumonia (CAP) is a major infectious disease threatening global child health. Its extrapulmonary complications can involve multiple systems, including the digestive, neurological, cardiovascular, hematological, and skin/mucous membrane systems, significantly increasing the risk of progression to severe illness and even death. The pathogenesis of extrapulmonary complications in pediatric CAP is complex and diverse, involving direct pathogen invasion, immune-mediated injury, inflammatory cytokine storm, and microcirculatory disorders, among which the interaction between immunity and inflammation is a core link. The pathogenic mechanisms vary among different pathogens, and the mutual promotion of immune-mediated injury and inflammatory cytokine storm is a central pathological process leading to multisystem extrapulmonary complications in severe CAP. Among digestive system complications, liver injury is the most common, with warning indicators including IL-1 > 28.35 pg/mL, IL-6 > 24.9 pg/mL, and CRP > 34.6 mg/L, while specific indicators exist for different pathogens (e.g., Mycoplasma pneumoniae, Chlamydia psittaci). Regarding nervous system complications, encephalitis, encephalopathy, and epileptic seizures are frequently observed, with warning indicators including neurofilament light chain (NFL), cerebrospinal fluid lactate, D-dimer, and lymphocyte count. Cardiovascular system complications are dominated by myocardial injury (incidence approximately 30.1%), with warning indicators including IL-6 ≥ 258.64 pg/mL, CRP ≥ 14.27 mg/L, and NLR ≥ 2.41; novel biomarkers such as sST2 and cfDNA also have value. Severe hematological complications, such as disseminated intravascular coagulation (DIC) and hemophagocytic lymphohistiocytosis (HLH), have warning indicators including LAR ≥ 8.08 and triglycerides > 3.02 mmol/L. Skin and mucous membrane lesions are mostly associated with Mycoplasma pneumoniae infection, presenting as rash and mucositis. At present, the warning indicators still require validation through multicenter studies with large samples, and most studies focus on Mycoplasma pneumoniae. In the future, comparative studies on complications caused by multiple pathogens and multi-omics research should be strengthened to establish a standardized assessment system.

关键词

儿童 / 社区获得性肺炎 / 肺外并发症 / 病理机制 / 危险因素

Key words

Pediatrics / Community-acquired pneumonia / Extrapulmonary complications / Pathological mechanism / Risk factors

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基金资助

重庆市自然科学基金(CSTB2025NSCQ-GPX0369)